Description: The goals of this investigation are to characterize the genetics of Essential Hyperhidrosis (EH), and to develop an improved understanding of the regulation of sweating by the autonomic nervous system. EH is a relatively common disorder in which patients' experience excessive sweating from their palms and soles. Patients with EH sweat profusely and, as a result, have difficulty with many activities of normal daily living, including social interactions, writing, using keyboards, and using musical instruments. It is not uncommon for the sweat to actually drip from the hands onto the floor. Many patients find EH so socially disabling and non-invasive therapies so ineffective that they undergo thoracic sympathectomy. The pathophysiology of EH is largely unknown; however, abundant evidence indicates that it is primarily a disorder of the autonomic nervous system. A genetic etiology and a dominant mode of inheritance have been suggested by several surgical studies, documenting a high-rate of affected first-degree family members, an equal number of affected male and female patients, and an early age-of-onset in nearly all patients. Despite this, no family study or report on the mode of inheritance of EH has ever been published. In addition, the control of sweating by the autonomic nervous system is poorly understood. We will recruit families with EH based on the identification of probands who have undergone thoracic sympathectomy. Detailed medical and family histories will be obtained, and a DNA sample will be collected from probands and family members. A state-of-the-art Skinos SKD-2000 skin moisture meter will be used to obtain measurements of resting and stimulated palmar, and forehead sweating from all study participants under a standardized protocol. The use of a specific questionnaire (the Hyperhidrosis Scale) and sweat measurements for the genetic investigation of EH will be validated. A detailed description of the EH phenotype will be developed, and a segregation analysis will be performed to determine the mode of inheritance. Simulation will be performed to determine the sample size and power for future linkage analysis. This will be followed by the mapping and cloning of the EH gene in follow-on studies. This study represents a rare opportunity to investigate a previously neglected neurogenetic condition. Knowledge of the gene responsible for EH will improve our understanding of the disease, and may permit the design of more effective therapies. Most importantly, understanding the etiology of EH may open a new window of understanding into the organization and regulation of the autonomic nervous system, and the regulation of body temperature and sweating.